Previous studies on stimulators of cellular contractility have been descriptive in nature primarily due to the lack of an appropriate model system. Because an extremely limited number of compounds stimulate myoepithelial cells, they provide a convenient model system and studies of the mechanisms of action of oxytocin in these cells should provide insight into the general mechanism of action of vasoactive polypeptides. Information obtained should have a bearing on health related problems such as hypertension and neuromuscular diseases. The objectives of this research proposal are fourfold: (1) To develop the myoepithelial cells as a model system for studying excitation-contraction coupling. (2) To characterize the contractile protein system of the myoepithelial cells and determine the mode of regulation. (3) To develop cell dispersion techniques for isolating the myoepithelial cells. (4) To determine the sequence of metabolic events which occur during excitation-contraction coupling in these cells. The specific approaches to be used in attaining these objectives will be to: (1) Develop a glycerinated mammary myoepithelium model comparable to the glycerinated muscle model and perform tension measurements, while carefully controlling the chemical environment of the contractile elements in the cells. (2) Perfuse the mammary glands of rabbits with enzymes to disperse the cells and then separate the secretory cells from the myoepithelial cells by centrifugation procedures. (3) Use the divalent ionophore A 23187 in conjunction with an ion buffer system to precisely control the intracellular ionic composition in living cells. (4) Determine whether phosphorylation of myosin or other contractile proteins occurs during excitation-contraction coupling. (5) Perform pilot experiments to determine the ionophoric potential of the cyclic polypeptide structure of oxytocin.